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Renal Physiology
Kidney Function
Regulation of water and inorganic ions
Excretion of metabolic waste products
Removing of foreign chemicals
ā€¢ producing ļ¹ excreting urine
ā€¢ so that maintain the internal
homeostasis of the body
1.
2.
3.
Kidney Function
4. Secretion of hormones
a. Erythropoietin (EPO --- is produced by
interstitial cells in peritubular capillary.),
which controls erythrocyte production
b. Renin, ( is produced by juxtaglomerular cell)
which controls formation of
1,25-dihydroxyvitamin D3 ,
Angiotensin II
c.
which influences calcium balance
Functional Anatomy of Kidneys and
Renal Circulation
Urinary system :
ļƒ˜ paired kidneys
ļƒ˜ paired ureters
ļƒ˜ a bladder
ļƒ˜ a urethra
Anatomical Characteristics of the Kidney
The kidney: renal
renal
renal
cortex
medulla
pelvis
Anatomical Characteristics of the Kidney
1. Nephrons: functional unit of kidneys
ā€¢ Nephron is the basic smallest functional unit
of kidney.
ā€¢ Nephron consists of renal corpuscle and renal
tubule.
Each kidney is composed of about 1 million
microscopic functional unit.
ā€¢
Nephron consists of..
glomerulus
renal corpuscle
Bowmanā€™s capsule
Nephron proximal convoluted tubule
proximal tubule
thick descending limb
thin descending limb
thin ascending limb
renal tubule thin segment loop of Henley
thick ascending limb
distal tubule
distal convoluted tubule
Anatomical Characteristics of the Kidney
Functional unit -nephron:
Corpuscle:
Bowmanā€™s capsule
Glomerulus capillaries
Tubule:
PCT
Loop of Henley
DCT
Collecting duct
Two Types of Nephron
ā€¢ Cortical nephrons
ā€¢
ā€¢
>85% of all nephrons
Located in the cortex
ā€¢ Juxtamedullary
nephrons
ā€¢ Closer to renal
medulla
Loops of Henle
deep into renal
pyramids
ā€¢ extend
Differences between a cortical and a Juxtamedullary nephron
Cortical nephron Juxtamedullary nephron
Location Outer part of the cortex Inner part of the cortex
next to the medulla
Big
Glomerulus Small
Loop of Henle Short, next to outer cortex Longer, into inner part of
cortex
AA= EA
T
o form Vasa recta
Diameter of AA* AA> EA
T
o form Peritubular capillary
EA
Sympathetic
nerve innervation
Concentration of renin
Rich Poor
High Almost no
Ratio
Function
90%
Reabsorption and secretion
10%
Concentrate and dilute
urine
* AA = afferent glomerular arteriole
** EA = efferent glomerular arteriole
Cortical and Juxtamedullary Nephrons
Juxtaglomerular apparatus consists
(JGA)
ļ¬ macula densa --- in initial portion of DCT
Function : sense change of volume and NaCl
concentration of tubular fluid , and transfer
information to JGC through paracrine
fashion
ļ¬ juxtaglomerular cell (JGC) --- in walls of the
arterioles)
Function: secrete renin
ļ¬ mesangial cellā€¦it functions as immunity
and GFR regulation
afferent
Juxaglomerular apparatus
JA locate in cortical nephron, consist of juxtaglomerular
cell态 mesangial cell and macula densa.
Tubulo-glomerular Feedback
Macula densa can detects Na+, K+ Cl-
ā€¢ and
of tubular fluid, and then sent some
information to glomerules, regulation
releasing of renin and glomerular filtration
rate. This process is called Tubulo-
glomerullar feedback.
Renal circulation
1.Characteristics of renal blood circulation
Huge volumes bloodļ¼š
1200ml/minļ¼Œ1/5 ā€“ 1/4
Distributionļ¼š
ā€¢
of the cardiac output.
ā€¢
Cortex 94%, outer medulla 5 - 6%, inner medulla
Two capillary beds:
<1%.
ā€¢
Renal arteryā†’interlobar arteries ā†’arcuate arteries
ā†’afferent arterioles ā†’glomerular capillaries ā†’efferent
arteriole ā†’peritubular capillaries ā†’arcuate vein
ā†’interlobar vein ā†’renal vein.
Renal circulation
ā€¢ Glomerular capillaries:
Higher pressure, benefit for filtration
ā€¢ Peritubular capillaries:
Lower pressure, benefit for reabsorption
Vasa recta
Concentrate and dilute urine
ā€¢
Renal circulation
Glomerular
capillary
Peritubular
capillary
cortex
medulla
vasa recta
Regulation of renal blood flow
(Autoregulation, neural, hormonal)
Autoregulation
When arterial pressure is in range of 80 to 180 mmHg, renal
blood flow (RBF) is relatively constant in denervated, isolated
or intact kidney.
Flow autoregulation is a major factor that controls RBF
Mechanism of autoregulation: myogenic theory of
autoregulation
Autoregulation of renal blood flow
Neural regulation
Renal sympathetic nerve
Activity of sympathetic nerve is low, but can increase
during hemorrhage, and stress.
Hormonal
Vasoconstriction
regulation
RBF
ā€¢
ā€¢
ā€¢
Angiotensin II
Epinephrine
Norepinephrine
Vasodilation RBF
ā€¢
ā€¢
ā€¢
Prostaglandin
nitrous oxide
Bradykinin
Basic processes for urine
Glomerular filtration:
Most substances in blood, except for protein
freely filtrated into Bowman's space.
Reabsorption:
formation
and cells, are
Water and specific solutes are reabsorbed
back into blood (peritubular capillaries).
Secretion:
from tubular fluid
Some substances (waste products, etc.) are secreted from
peritubular capillaries or tubular cell interior into tubules.
Amount Excreted = Amount filtered ā€“ Amount reabsorbed +
Amount secreted
Three basic processes of the formation of urine.
Basic processes for urine formation
Glomerular filtration, reabsorption,
secretion
Glomerular Filtration
Only water and small solutes can be filtrated----selective.
Composition of the glomerular filtrates
Except for proteins, the composition of glomerular filtrates
same as that of plasma.
is
Figure 26.10a, b
Glomerular filtration membrane
The barrier between the
capillary blood and the
fluid in the Bowmanā€™s
space.
Composition: three layers
Capillary endothelium ---
fenestrations(70-90nm)
Basement membrane ---
meshwork
Epithelial cells (podocyte)
--slit pores
ā€¢
ā€¢
ā€¢ -
Showing the filtration membran. To be filtered, a substance must pass
through 1. the pores between the endothelial cells of the glomerullar capillary,
2. cellular basement membrane, and 3. the filtration slits between the foot
processes of the podocytes of the inner layer of Bowmanā€™s capsule.
Selective permeability
membrane
of filtration
Structure Characteristics:
There are many micropores in each layer
Each layer contains negatively charged glycoproteins
Selective permeability
membrane
of filtration
Size selection :
impermeable to substances
with high molecular weight
Charge selection :
Repel negative charged substances
Filtrate Composition
Glomerular filtration barrier restricts the filtration of
molecules on the basis of size and electrical charge
Neutral solutes:
ā€¢
ā€¢
ā€¢ Solutes
filtered
Solutes
smaller than 180 nanometers in radius are freely
ā€¢
ā€¢
greater than 360 nanometers do not
Solutes between 180 and 360 nm are filtered to various
degrees
ā€¢ Serum albumin is anionic and has a 355 nm radius,
only ~7 g is filtered per day (out of ~70 g/day passing
through glomeruli)
In a number of glomerular diseases, the negative
charge on various barriers for filtration is lost due to
immunologic damage and inflammation, resulting in
proteinuria (i.e. increased filtration of serum proteins
that are mostly negatively charged).
ā€¢
Filtration Coefficient ( Kf )
ā€¢ Filtration coefficient is a minute volume of
plasma filtered through the filtration
membrane by unit effective filtration pressure
drive. Kf =KƗS
GFR is dependent on the filtration coefficient
as well as on the net filtration pressure.
GFR=PƗ Kf
The surface area and the permeability of the
ā€¢
ā€¢
glomerular membrane can affect Kf.
Regulation of Glomerular Filtration
If the GFR is too high, needed substances cannot
be reabsorbed quickly enough and are lost in the
urine
If the GFR is too low - everything is reabsorbed,
including wastes that are normally disposed of
Control of GFR normally result from adjusting
glomerular capillary blood pressure
Three mechanisms control the GFR
ā€¢
ā€¢
ā€¢
ā€¢
ā€¢
ā€¢
ā€¢
Renal autoregulation (intrinsic system)
Neural controls
Hormonal mechanism (the renin-angiotensin system)
Autoregulation of GFR
ā€¢ Under normal conditions (MAP =80-180mmHg) renal
maintains a nearly constant glomerular filtration rate
Two mechanisms are in operation for autoregulation:
autoregulation
ā€¢
ā€¢
ā€¢
Myogenic mechanism
Tubuloglomerular feedback
ā€¢ Myogenic mechanism:
ā€¢
ā€¢
ā€¢
Arterial pressure rises, afferent arteriole stretches
Vascular smooth muscles contract
Arteriole resistance offsets pressure increase; RBF (& hence
remain constant.
GFR)
ā€¢ Tubuloglomerular feed back mechanism for autoregulation:
ā€¢ Feedback loop consists of a flow rate (increased NaCl) sensing
mechanism in macula densa of juxtaglomerular apparatus (JGA)
Increased GFR (& RBF) triggers release of vasoactive signals
Constricts afferent arteriole leading to a decreased GFR (& RBF)
ā€¢
ā€¢
Extrinsic Controls
When the sympathetic nervous system is at
ā€¢ rest:
ā€¢
ā€¢
Renal blood vessels are maximally dilated
Autoregulation mechanisms prevail
ā€¢ Under stress:
ā€¢
ā€¢
ā€¢
Norepinephrine is released by the sympathetic nervous
Epinephrine is released by the adrenal medulla
Afferent arterioles constrict and filtration is inhibited
system
ā€¢ The sympathetic nervous system also stimulates
renin-angiotensin mechanism
the
ā€¢ A drop in filtration pressure stimulates the
Juxtaglomerular apparatus (JGA) to release renin
Response to a Reduction in the GFR
Renin-Angiotensin Mechanism
Renin release is triggered by:
ā€¢
ā€¢
ā€¢
ā€¢
Reduced stretch of the granular JG cells
Stimulation of the JG cells by activated macula densa cells
Direct stimulation of the JG cells via ļ¢1-adrenergic receptors
renal nerves
by
ā€¢ Renin acts on angiotensinogen to release angiotensin
which is converted to angiotensin II
Angiotensin II:
I
ā€¢
ā€¢
ā€¢
Causes mean arterial pressure to rise
Stimulates the adrenal cortex to release aldosterone
ā€¢ As a result, both systemic and glomerular hydrostatic
pressure rise
Other Factors Affecting Glomerular Filtration
ā€¢ Prostaglandins (PGE2 and PGI2)
ā€¢ Vasodilators produced in response to sympathetic
stimulation and angiotensin II
Are thought to prevent renal damage when peripheral
resistance is increased
ā€¢
ā€¢ Nitric oxide ā€“ vasodilator produced by the
vascular endothelium
Adenosine ā€“ vasodilator of renal vasculature
Endothelin ā€“ a powerful vasoconstrictor secreted
by tubule cells
ā€¢
ā€¢
Control of Kf
Mesangial cells have contractile properties, influence
capillary filtration by closing some of the capillaries ā€“
effects surface area
Podocytes change size of filtration slits
ā€¢
ā€¢
Process of Urine Formation
ā€¢
ā€¢
Glomerular filtration
Tubular reabsorption of
the substance from the
tubular fluid into blood
Tubular secretion of the
substance from the blood
into the tubular fluid
Mass Balance
ā€¢
ā€¢
ā€¢ Amount Excreted in Urine =
Amount Filtered through
glomeruli into renal proximal
tubule MINUS amount
reabsorbed into capillaries
PLUS amount secreted into
the tubules
Tubular Secretion
ā€¢ substances move from peritubular capillaries
tubule cells into filtrate
Tubular secretion is important for:
or
ā€¢
ā€¢
Disposing of substances not already in the filtrate
Eliminating undesirable substances such as urea
uric acid
Ridding the body of excess potassium ions
Controlling blood pH
and
ā€¢
ā€¢
Tubular reabsorption and secretion
Tubular processing of urine formation
Characteristics and mechanism of reabsorption and
secretion
Characteristics of reabsorption:
quantitatively large
More than 99% volume of filtered fluid are reabsorbed
(> 178L).
selective
100% glucose, 99% sodium and chloride, 85%
bicarbonate are reabsorbed
Urea and creatinine are partly reabsorbed.
Type of transportation in renal tubule and
colllecting duct
ā€¢
ā€¢
Transportation mechanisms For Reabsorption
and secretion
Passive reabsorption (with out energy)
Diffusion, osmosis, facilitated diffusion
Active reabsorption (need energy)
Sodium pump (Na+-K+ ATPase), proton pump (H+-
ATPase), calcium pump (Ca2+-ATPase).
Cotransport (coupled transport):
ā€¢
ā€¢
ā€¢
One transportor can transport two or more substances.
ā€¢ Symport transport:
Antiport transport:
like Na+ and glucose, Na+ and amino acids
like Na+-H+ and Na+-K+
ā€¢ Secondary active transport : like H+ secretion
Na+ active transport in PT epithelium
ā€¢ Passway of transport
Apical membrane, tight
basolateral membrane
Transcellular pathway
juction, brush border,
ā€¢
Na+ epithelium
apical membrane Na+ pump peritubular
capillary
Paracellular transport
ā€¢
Water, Cl- and Na+ tight juction peritubular capillary
K+ Ca2+
and are reabsorpted with water by solvent drag
The pathway of reabsorption
Reabsorption of transcellular and paracellular pathway
Location of reabsorption
(Every parts of Nephron)
ļ‚” Proximal tubule
Brush border can
reabsorption
ļ‚” Henle's loop
ļ‚” Distal tubule
ļ‚” Collecting duct
increase the area of
Reabsorption and secretion in different part
renal tubule
of
ā€¢ Proximal tubule (PT)
67% Na+, Cl-, K+ and water; 85% HCO3
- and 100%
glucose and amino acids are reabsorbed
H+
secretion
2/3 Transcellular pathway
1/3 Paracellular transport
The key of reabsorption is Na+ reabsorption ( the
action of Na+ pump in the membrane of proximal
tubule).
Na+ transcellular transportation in early part of PT epithelium
Cl- passive reabsorption in later part of PT epithelium
K+ reabsorption
ļ‚” Most of in PT (70%)ļ¼Œ20%
ļ‚” Active reabsorption
in loop of Henle
Ca2+ reabsorption
ļ‚” 70% in PT
, 20% in loop of Henle, 9% in DCT
Bicarbonate reabsorption
Glucose and amino acid reabsorption
Glucose reabsorption:
99% glucose are reabsorbed, no glucose in urine
ā€¢ Location:
early part of PT
Type of reabsorption:
secondary active transport
Renal glucose threshold
When the plasma glucose concentration
ā€¢
ā€¢
increases up to a
value about 160 to 180 mg per deciliter, glucose can first
be detected in the urine, this value is called the renal
glucose threshold.
Glucose secondary active transport in early part of PT
Transport maximum (Tm)
Transport maximum is the maximum rate at which
the kidney active
particular
transport
solute
mechanisms can
the
transfer
tubules.
a into or out of
Amino acid reabsorption:
Location and type of reabsorption as same
glucose
as
Glucose secondary active transport in early part of PT
Co-transport of amino acids via Na+ symport mechanism.
Loop of Henle:
Ascending thick limb of loop of Henle
Na+, Cl- and K+ cotransport
Transportation rate: Na+ : 2Cl- : K+
Distal tubule and collecting duct:
Principal cell: Reabsorption Na+ water and
K+
secretion
Intercalated cell: Secretion H+
Secretion at the DCT
ā€¢
ā€¢
DCT performs final adjustment of urine
Active secretion or absorption
Absorption of Na+ and Cl-
Secretion of K+ and H+ based on blood pH
ā€¢
ā€¢
ā€¢
ā€¢
Water is regulated by ADH (vasopressin)
Na+, K+ regulated by aldosterone
K+ H+
and secretion in distal tubule and collecting duct
Co-transport of amino acids via Na+ symport mechanism.
Summary of transport across PT
, DT and collecting duct
Proximal tubule
Reabsorption Secretion
filtered Na+ actively reabsorbed; Cl-
follows passively.
All filtered glucose and amino acids
reabsorbed by secondary active
transport,
Filtered H2Oosmoticallyreabsorbed,
Almost all filtered K+ reabsorbed,
H+
Variable secretion,
depending on acid-base
status of body.
Distal tubule and collecting duct
Reabsorption Secretion
Variable Na+ reabsorbed
Aldosterone;
Cl- follows passively. Variable
H2O reabsorption, controlled by
vasopressin (ADH)
Variable H+ secretion,
depending on acid-base
status of body.
by
K+
Variable secretion,
controlled by aldosterone.
Urinary Concentration and Dilution
Hypertonic urine:
Lack of water in body can forms concentrated urine
(1200 mOsm/L).
Hypotonic urine:
More water in body can forms dilute urine (50 mOsm/L).
Isotonic urineļ¼šInjury of renal function
Urinary dilution:
The mechanism for forming a dilute urine is continuously reabsorbing
reabsorb water.
Urinary concentration:
The basic requirements for forming a concentrated urine are a high
fluid.
ā€¢
ā€¢
ā€¢
ā€¢
solutes from the distal segments of the tubular system while failing to
ā€¢
level of ADH and a high osmolarity of the renal medullary interstitial
formation of dilute and concentrated urine.
Control of Urine Volume and Concentration
ā€¢ Urine volume and osmotic concentration are regulated
by controlling water and sodium reabsorption
Precise control allowed via facultative water reabsorption
Osmolality
ā€¢
ā€¢
ā€¢
ā€¢
The number of solute particles dissolved in 1L of water
Reflects the solutionā€™s ability to cause osmosis
ā€¢
ā€¢
Body fluids are measured in milliosmols (mOsm)
The kidneys keep the solute load of body fluids constant
at about 300 mOsm
This is accomplished by the countercurrent mechanism
ā€¢
ļ‚” Formation of concentrated and diluted urine
Drink more water
in DCT and CD
Lack of water
in DCT and CD
ADH
diluted
ADH
water reabsorption
urine.
water reabsorption
concentrated urine.
ļ‚” Role of the vasa recta for maintaining the
high solute concentration (NaCl and urea)
in the medullary interstitial fluid.
Role of countercurrent exchanger
Urinary concentrating environment.
ā€¢ Basic structureļ¼š
ā€œUā€type of loop of Henle
Vasa rectaā€™s cliper type
Collecting duct from cortex to medulla
ā€¢ Basic functionļ¼š
Different permeability of solutes and water
DCT, CD and loop of Henle.
in
ā€¢ Osmotic gradient exit from cortex to medulla.
Permeabilities of different segments of the renal tubule
Segments of
renal tubule
Permeability
water
to Permeability to
Na+
Permeability
urea
to
Thick ascending
limb
Almost not Active transport of
Na+, Secondary
Almost not
Cl-
active Transport of
Thin ascending
limb
Almost not Yes Moderate
Almost not Almost not
Thin descending
limb
Yes
K+
Distal convoluted
tubule
Permeable
Under ADH
action
Secretion of Almost not
K+-Na+ exchange
Collecting
duct
Cortex and outer
Medulla almost not
Inner medulla Yes
Permeable
Under ADH
action
Yes
ļ‚” Mechanisms for creating osmotic gradient in the
medullary interstitial fluid
ļ‚” Formation of osmotic gradient is related to
physiological characters of each part of renal tubule.
ļ‚” Outer medullaļ¼š
Water are permeated in descending thin limb, but not NaCl
and urea.
NaCl and urea are
not water.
permeated in ascending thin limb, but
NaCl is active reabsorbed in ascending thick limb, but not
Urea and water.
ļ‚” Formation of osmotic gradient in outer medulla is
due to NaCl active reabsorption in outer medulla.
Inner medullaļ¼š
High concentration urea exit in tubular fluid.
ā€¢
ā€¢
ā€¢ Urea is permeated in CD of inner medulla
in cortex and outer medulla
NaCl is not permeated in descending thin
NaCl is permeated in ascending thin limb
Urea recyclingļ¼š
but not
ā€¢
ā€¢
ā€¢
ā€¢
limb
Urea is permeated in ascending thin limb, part of urea into
ascending thin limb from medulla and then diffusion to
interstitial fluid again.
Formation of osmotic gradient in inner medulla is
due to urea recycling and NaCl passive diffusion in inner
medulla.
ā€¢
Countercurrent Mechanism
Interaction between the flow of filtrate through the loop of Henle
(countercurrent multiplier) and the flow of blood through the vasa
recta blood vessels (countercurrent exchanger)
The solute concentration in the loop of Henle ranges from 300
mOsm to 1200 mOsm
ā€¢
ā€¢
ļ® Countercurrent exchange
Countercurrent exchange is a common process in
the vascular system. Blood flows in opposite
directions along juxtaposed decending (arterial) and
ascending (venous) vasa recta, and solutes and water
are Exchanged between these capillary blood vessels.
ļ® Countercurrent multiplication
Countercurrent multiplication is the process where
by a small gradient established at any level of the
loop of Henle is increased (maltiplied) into a much
larger gradient along the axis of the loop.
Loop of Henle: Countercurrent Multiplication
Vasa Recta prevents loss of medullary osmotic gradient equilibrates with
the interstitial fluid
ā€¢
ā€¢
ā€¢
Maintains the osmotic gradient
Delivers blood to the cells in the area
ā€¢ The descending loop: relatively impermeable to solutes, highly permeable to
water
The ascending loop: permeable to solutes, impermeable to water
Collecting ducts in the deep medullary regions are permeable to urea
ā€¢
ā€¢
Countercurrent Multiplier and Exchange
ā€¢ Medullary
gradient
osmotic
ā€¢ H2Oļ‚®ECFļ‚®vasa recta
vessels
Formation of Concentrated
ADH (ADH) is the
signal to produce
Urine
ā€¢
concentrated urine
inhibits diuresis
This equalizes the
osmolality of the
filtrate and the
interstitial fluid
In the presence of
ADH, 99% of the
water in filtrate is
reabsorbed
it
ā€¢
ā€¢
Formation of Dilute Urine
ā€¢ Filtrate is diluted in the ascending
loop of Henle if the antidiuretic
hormone (ADH) or vasopressin is not
secreted
Dilute urine is created by allowing this
filtrate to continue into the renal pelvis
Collecting ducts remain impermeable
to water; no further water
reabsorption occurs
Sodium and selected ions can be
removed by active and passive
mechanisms
Urine osmolality can be as low as 50
mOsm (one-sixth that of plasma)
ā€¢
ā€¢
ā€¢
ā€¢
Figure 20-6: The mechanism of action of
Mechanism of ADH (Vasopressin) Action:
Formation of Water Pores
ā€¢ ADH-dependent water reabsorption is called facultative
water reabsorption
vasopressin
Water Balance Reflex:
Regulators of Vasopressin Release
Figure 20-7: Factors affecting vasopressin release
Regulation of Urine Formation in the Kidney
Way of regulation for urine formationļ¼š
Filtration, Reabsorption and Secretion
ā€¢
ā€¢
ā€¢
Autoregulation
Solute concentration of tubular fluid
Osmotic diuresis -- diabatic态mannitol
Glomerulotubular balance
ā€¢
ļ‚” Nervous regulation
ļ‚” Role of Renal Sympathetic Nerve
ļ‚” Reflex of renal sympathetic nerve
Reflex of cardiopumonary receptor
renorenal reflex
ļ‚” Renin-angiotention-aldosterone system
Renin-Angiotension-Aldosterone System
Regulation by ADH
ā€¢ Released by posterior
pituitary when
osmoreceptors detect
an increase in plasma
osmolality.
Dehydration or excess
salt intake:
ā€¢
ā€¢ Produces sensation
of thirst.
Stimulates H20
reabsorption from
urine.
ā€¢
The regulation of ADH secretion
ļ¬ Source of ADH
Hypothalamus supraoptic and
paraventricular nuclei
The change of crystal
pressure
osmotic
Effective stimuli
The change of effective blood
volume
Source of ADH
Effects of ADH on the DCT and Collecting Ducts
Figure 26.15a, b
Regulation of ADH release: over hydration
Regulation of release: hypertonicity
Atrial Natriuretic Peptide Activity
ļ¬ Increase GFR , reducing water reabsorption
ļ¬ Decrease the osmotic gradient of renal medulla
and promotes Na+ excretion
ļ¬ Acting directly on collecting ducts to inhibit Na+
and water reabsorption, promotes Na+ and
water excretion in the urine by the kidney
ļ¬ Inhibition renin release and decrease
angiotensin II and aldosterone, promotes Na+
excretion
ļ‚” Endothelin (ET)
Constriction blood vessels, decrease GFR
ļ‚” Nitic Oxide (NO)
Dilation blood vessels, increase GFR
ļ‚” Epinephrine (EP), Norepinephrine (NE)
promote Na+ and water reabsorption
ļ‚” Prostaglandin E2 ,I2
Dilation blood vessels, excretion Na+ and water.
A Summary of Renal Function
Figure 26.16a
Renal clearance
1. Concept:
Renal clearance of any substance is the volume of
plasma that is completely cleaned of the substance
the kidneys per unit time (min)
2. Calculate
concentration of it in urine Ɨurine volume
by
C =
concentration of it in plasma
Renal Clearance
RC = UV/P
RC = renal clearance rate
U = concentration (mg/ml) of the substance in urine
V = flow rate of urine formation (ml/min)
P = concentration of the same substance
Renal clearance tests are used to:
in plasma
ā€¢
ā€¢ Determine the GFR
ā€¢
ā€¢
Detect glomerular damage
Follow the progress of diagnosed renal disease
Theoretical significance of clearance
3.1 Measure GFR
ā€¢ A substance---freely filtered, non reabsorbed,
non secreted--its renal clearance = GFR
Clearance of inulin or creatinine can be used to
estimate GFR
ā€¢
3.2 Calculate RPF and RBF
A substance--freely filtered, non reabsorbed, secreted
completely from peritubular cells ---a certain
concentration in renal arteries and 0 in venous.
Clearance of para-aminohippuric acid (PAH) or diodrast
can be used to calculate RPF
.
3.3 Estimate of tubular handling for a substance
If the clearance of substance>125ml/min?
---it must be secreted
If it <125ml/min? --- it must be reabsorbed
Physical Characteristics of Urine
ļ¬ Color and transparency
ā€¢
ā€¢
ā€¢
Clear, pale to deep yellow (due to urochrome)
Concentrated urine has a deeper yellow color
Drugs, vitamin supplements, and diet can change the color
urine
of
ā€¢
pH
ā€¢
ā€¢
Cloudy urine may indicate infection of the urinary tract
ļ¬
Slightly acidic (pH 6) with a range of 4.5 to 8.0
Diet can alter pH
ļ¬ Specific gravity
ā€¢
ā€¢
Ranges from 1.001 to 1.035
Is dependent on solute concentration
Chemical Composition of Urine
ā€¢
ā€¢
Urine is 95% water and 5% solutes
Nitrogenous wastes include urea, uric acid,
creatinine
Other normal solutes include:
and
ā€¢
ā€¢
ā€¢
Sodium, potassium, phosphate, and sulfate ions
Calcium, magnesium, and bicarbonate ions
ā€¢ Abnormally high concentrations of any urinary
constituents may indicate pathology
Urine Volume and Micturition
1. Urine volume
ļ¬
ļ¬
Normal volume : 1.0~2.0L/day
Obligatory urine volume ~400ml/day
Minimum needed to excrete metabolic wastes of
waste products in body.
ļ¬
ļ¬
Oliguria--- urine volume < 400ml/day
Anuria---urine volume < 100ml/day
Accumulation of waste products in body. Polyuria---
urine volume > 2500ml/day long time Abnormal urine
volume: Losing water and electrolytes.
ļ¬
Micturition
Functions of ureters and bladder:
Urine flow through ureters to bladder is
propelled by contractions of ureter-wall
smooth muscle.
Urine is stored in bladder and intermittently
ejected during urination, or micturition.
Micturition
ā€¢ Micturition is process of emptying
urinary bladder
Two steps are involved:
the
ā€¢
ā€¢ (1) bladder is filled progressively
pressure rises
until its
ā€¢
ā€¢
above a threshold level (400~500ml);
(2) a nervous reflex called micturition
reflex occurs that empties bladder.
Micturition
ā€¢ Pressure-Volume curve of the bladder has
a characteristic shape.
There is a long flat segment as the initial
increments of urine enter the bladder and
then a sudden sharp rise as the micturition
reflex is triggered.
ā€¢
Pressure-volume graph for
bladder
normal human
1.25
1.00
Sense of
0.75
0.50
0.25
100 200 300 400
Volume (ml)
Pressure
(kPa)
Discomfort
1st desire urgency
to empty
bladder
Micturition (Voiding or Urination)
ā€¢
ā€¢
Bladder can hold 250 - 400ml
Greater volumes stretch bladder walls initiates
micturation reflex:
Spinal reflex
ā€¢
ā€¢ Parasympathetic stimulation
contract
Internal sphincter opens
causes bladder to
ā€¢
ā€¢ External sphincter relaxes due to inhibition
Innervation of bladder
Urination: Micturation reflex
Figure 19-18: The micturition reflex
Figure 25
Micturition (Voiding or Urination)
.20a, b
Review Questions
Explain concepts
1.Glomerular filtration rate
2. Effective filtration pressure
3. Filtration fraction
4.Renal glucose threshold
5.Osmotic diuresis
6.Renal clearance
Review Questions
the functions of the kidneys?
autoregulation of renal plasma
1. What are
2. Describe
flow.
3. What are three basic processes for urine
formation?
4. Describe the forces affecting glomerular
filtration.
5. Describe the factors affecting GFR.
6. What is the mechanism of sodium
reabsorption in the proximal tubules ?
Review Questions
7. What is the mechanism of hydrogen ion
secretion and bicarbonate reabsorption?
What is the mechanism of formation of
concentrated and diluted urine?
After drinking large amount of water, what does
8.
9.
the amount of urine change? Why?
10. Why a patient with diabetes has glucosuria and
polyuria?

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A RENAL ppt.pptx

  • 2.
  • 3. Kidney Function Regulation of water and inorganic ions Excretion of metabolic waste products Removing of foreign chemicals ā€¢ producing ļ¹ excreting urine ā€¢ so that maintain the internal homeostasis of the body 1. 2. 3.
  • 4. Kidney Function 4. Secretion of hormones a. Erythropoietin (EPO --- is produced by interstitial cells in peritubular capillary.), which controls erythrocyte production b. Renin, ( is produced by juxtaglomerular cell) which controls formation of 1,25-dihydroxyvitamin D3 , Angiotensin II c. which influences calcium balance
  • 5. Functional Anatomy of Kidneys and Renal Circulation Urinary system : ļƒ˜ paired kidneys ļƒ˜ paired ureters ļƒ˜ a bladder ļƒ˜ a urethra
  • 6. Anatomical Characteristics of the Kidney The kidney: renal renal renal cortex medulla pelvis
  • 7. Anatomical Characteristics of the Kidney 1. Nephrons: functional unit of kidneys ā€¢ Nephron is the basic smallest functional unit of kidney. ā€¢ Nephron consists of renal corpuscle and renal tubule. Each kidney is composed of about 1 million microscopic functional unit. ā€¢
  • 8. Nephron consists of.. glomerulus renal corpuscle Bowmanā€™s capsule Nephron proximal convoluted tubule proximal tubule thick descending limb thin descending limb thin ascending limb renal tubule thin segment loop of Henley thick ascending limb distal tubule distal convoluted tubule
  • 9.
  • 10. Anatomical Characteristics of the Kidney Functional unit -nephron: Corpuscle: Bowmanā€™s capsule Glomerulus capillaries Tubule: PCT Loop of Henley DCT Collecting duct
  • 11. Two Types of Nephron ā€¢ Cortical nephrons ā€¢ ā€¢ >85% of all nephrons Located in the cortex ā€¢ Juxtamedullary nephrons ā€¢ Closer to renal medulla Loops of Henle deep into renal pyramids ā€¢ extend
  • 12. Differences between a cortical and a Juxtamedullary nephron Cortical nephron Juxtamedullary nephron Location Outer part of the cortex Inner part of the cortex next to the medulla Big Glomerulus Small Loop of Henle Short, next to outer cortex Longer, into inner part of cortex AA= EA T o form Vasa recta Diameter of AA* AA> EA T o form Peritubular capillary EA Sympathetic nerve innervation Concentration of renin Rich Poor High Almost no Ratio Function 90% Reabsorption and secretion 10% Concentrate and dilute urine * AA = afferent glomerular arteriole ** EA = efferent glomerular arteriole
  • 14. Juxtaglomerular apparatus consists (JGA) ļ¬ macula densa --- in initial portion of DCT Function : sense change of volume and NaCl concentration of tubular fluid , and transfer information to JGC through paracrine fashion ļ¬ juxtaglomerular cell (JGC) --- in walls of the arterioles) Function: secrete renin ļ¬ mesangial cellā€¦it functions as immunity and GFR regulation afferent
  • 15. Juxaglomerular apparatus JA locate in cortical nephron, consist of juxtaglomerular cell态 mesangial cell and macula densa.
  • 16. Tubulo-glomerular Feedback Macula densa can detects Na+, K+ Cl- ā€¢ and of tubular fluid, and then sent some information to glomerules, regulation releasing of renin and glomerular filtration rate. This process is called Tubulo- glomerullar feedback.
  • 17. Renal circulation 1.Characteristics of renal blood circulation Huge volumes bloodļ¼š 1200ml/minļ¼Œ1/5 ā€“ 1/4 Distributionļ¼š ā€¢ of the cardiac output. ā€¢ Cortex 94%, outer medulla 5 - 6%, inner medulla Two capillary beds: <1%. ā€¢ Renal arteryā†’interlobar arteries ā†’arcuate arteries ā†’afferent arterioles ā†’glomerular capillaries ā†’efferent arteriole ā†’peritubular capillaries ā†’arcuate vein ā†’interlobar vein ā†’renal vein.
  • 18. Renal circulation ā€¢ Glomerular capillaries: Higher pressure, benefit for filtration ā€¢ Peritubular capillaries: Lower pressure, benefit for reabsorption Vasa recta Concentrate and dilute urine ā€¢
  • 20. Regulation of renal blood flow (Autoregulation, neural, hormonal) Autoregulation When arterial pressure is in range of 80 to 180 mmHg, renal blood flow (RBF) is relatively constant in denervated, isolated or intact kidney. Flow autoregulation is a major factor that controls RBF Mechanism of autoregulation: myogenic theory of autoregulation
  • 22. Neural regulation Renal sympathetic nerve Activity of sympathetic nerve is low, but can increase during hemorrhage, and stress.
  • 24. Basic processes for urine Glomerular filtration: Most substances in blood, except for protein freely filtrated into Bowman's space. Reabsorption: formation and cells, are Water and specific solutes are reabsorbed back into blood (peritubular capillaries). Secretion: from tubular fluid Some substances (waste products, etc.) are secreted from peritubular capillaries or tubular cell interior into tubules. Amount Excreted = Amount filtered ā€“ Amount reabsorbed + Amount secreted
  • 25. Three basic processes of the formation of urine.
  • 26. Basic processes for urine formation Glomerular filtration, reabsorption, secretion
  • 27. Glomerular Filtration Only water and small solutes can be filtrated----selective.
  • 28. Composition of the glomerular filtrates Except for proteins, the composition of glomerular filtrates same as that of plasma. is
  • 29. Figure 26.10a, b Glomerular filtration membrane The barrier between the capillary blood and the fluid in the Bowmanā€™s space. Composition: three layers Capillary endothelium --- fenestrations(70-90nm) Basement membrane --- meshwork Epithelial cells (podocyte) --slit pores ā€¢ ā€¢ ā€¢ -
  • 30. Showing the filtration membran. To be filtered, a substance must pass through 1. the pores between the endothelial cells of the glomerullar capillary, 2. cellular basement membrane, and 3. the filtration slits between the foot processes of the podocytes of the inner layer of Bowmanā€™s capsule.
  • 31. Selective permeability membrane of filtration Structure Characteristics: There are many micropores in each layer Each layer contains negatively charged glycoproteins
  • 32. Selective permeability membrane of filtration Size selection : impermeable to substances with high molecular weight Charge selection : Repel negative charged substances
  • 33. Filtrate Composition Glomerular filtration barrier restricts the filtration of molecules on the basis of size and electrical charge Neutral solutes: ā€¢ ā€¢ ā€¢ Solutes filtered Solutes smaller than 180 nanometers in radius are freely ā€¢ ā€¢ greater than 360 nanometers do not Solutes between 180 and 360 nm are filtered to various degrees ā€¢ Serum albumin is anionic and has a 355 nm radius, only ~7 g is filtered per day (out of ~70 g/day passing through glomeruli) In a number of glomerular diseases, the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation, resulting in proteinuria (i.e. increased filtration of serum proteins that are mostly negatively charged). ā€¢
  • 34.
  • 35.
  • 36.
  • 37.
  • 38.
  • 39.
  • 40.
  • 41.
  • 42.
  • 43. Filtration Coefficient ( Kf ) ā€¢ Filtration coefficient is a minute volume of plasma filtered through the filtration membrane by unit effective filtration pressure drive. Kf =KƗS GFR is dependent on the filtration coefficient as well as on the net filtration pressure. GFR=PƗ Kf The surface area and the permeability of the ā€¢ ā€¢ glomerular membrane can affect Kf.
  • 44. Regulation of Glomerular Filtration If the GFR is too high, needed substances cannot be reabsorbed quickly enough and are lost in the urine If the GFR is too low - everything is reabsorbed, including wastes that are normally disposed of Control of GFR normally result from adjusting glomerular capillary blood pressure Three mechanisms control the GFR ā€¢ ā€¢ ā€¢ ā€¢ ā€¢ ā€¢ ā€¢ Renal autoregulation (intrinsic system) Neural controls Hormonal mechanism (the renin-angiotensin system)
  • 45. Autoregulation of GFR ā€¢ Under normal conditions (MAP =80-180mmHg) renal maintains a nearly constant glomerular filtration rate Two mechanisms are in operation for autoregulation: autoregulation ā€¢ ā€¢ ā€¢ Myogenic mechanism Tubuloglomerular feedback ā€¢ Myogenic mechanism: ā€¢ ā€¢ ā€¢ Arterial pressure rises, afferent arteriole stretches Vascular smooth muscles contract Arteriole resistance offsets pressure increase; RBF (& hence remain constant. GFR) ā€¢ Tubuloglomerular feed back mechanism for autoregulation: ā€¢ Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA) Increased GFR (& RBF) triggers release of vasoactive signals Constricts afferent arteriole leading to a decreased GFR (& RBF) ā€¢ ā€¢
  • 46. Extrinsic Controls When the sympathetic nervous system is at ā€¢ rest: ā€¢ ā€¢ Renal blood vessels are maximally dilated Autoregulation mechanisms prevail ā€¢ Under stress: ā€¢ ā€¢ ā€¢ Norepinephrine is released by the sympathetic nervous Epinephrine is released by the adrenal medulla Afferent arterioles constrict and filtration is inhibited system ā€¢ The sympathetic nervous system also stimulates renin-angiotensin mechanism the ā€¢ A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin
  • 47. Response to a Reduction in the GFR
  • 48. Renin-Angiotensin Mechanism Renin release is triggered by: ā€¢ ā€¢ ā€¢ ā€¢ Reduced stretch of the granular JG cells Stimulation of the JG cells by activated macula densa cells Direct stimulation of the JG cells via ļ¢1-adrenergic receptors renal nerves by ā€¢ Renin acts on angiotensinogen to release angiotensin which is converted to angiotensin II Angiotensin II: I ā€¢ ā€¢ ā€¢ Causes mean arterial pressure to rise Stimulates the adrenal cortex to release aldosterone ā€¢ As a result, both systemic and glomerular hydrostatic pressure rise
  • 49.
  • 50. Other Factors Affecting Glomerular Filtration ā€¢ Prostaglandins (PGE2 and PGI2) ā€¢ Vasodilators produced in response to sympathetic stimulation and angiotensin II Are thought to prevent renal damage when peripheral resistance is increased ā€¢ ā€¢ Nitric oxide ā€“ vasodilator produced by the vascular endothelium Adenosine ā€“ vasodilator of renal vasculature Endothelin ā€“ a powerful vasoconstrictor secreted by tubule cells ā€¢ ā€¢
  • 51. Control of Kf Mesangial cells have contractile properties, influence capillary filtration by closing some of the capillaries ā€“ effects surface area Podocytes change size of filtration slits ā€¢ ā€¢
  • 52.
  • 53. Process of Urine Formation ā€¢ ā€¢ Glomerular filtration Tubular reabsorption of the substance from the tubular fluid into blood Tubular secretion of the substance from the blood into the tubular fluid Mass Balance ā€¢ ā€¢ ā€¢ Amount Excreted in Urine = Amount Filtered through glomeruli into renal proximal tubule MINUS amount reabsorbed into capillaries PLUS amount secreted into the tubules
  • 54. Tubular Secretion ā€¢ substances move from peritubular capillaries tubule cells into filtrate Tubular secretion is important for: or ā€¢ ā€¢ Disposing of substances not already in the filtrate Eliminating undesirable substances such as urea uric acid Ridding the body of excess potassium ions Controlling blood pH and ā€¢ ā€¢
  • 56. Tubular processing of urine formation Characteristics and mechanism of reabsorption and secretion Characteristics of reabsorption: quantitatively large More than 99% volume of filtered fluid are reabsorbed (> 178L). selective 100% glucose, 99% sodium and chloride, 85% bicarbonate are reabsorbed Urea and creatinine are partly reabsorbed.
  • 57. Type of transportation in renal tubule and colllecting duct ā€¢ ā€¢ Transportation mechanisms For Reabsorption and secretion Passive reabsorption (with out energy) Diffusion, osmosis, facilitated diffusion Active reabsorption (need energy) Sodium pump (Na+-K+ ATPase), proton pump (H+- ATPase), calcium pump (Ca2+-ATPase). Cotransport (coupled transport): ā€¢ ā€¢ ā€¢ One transportor can transport two or more substances. ā€¢ Symport transport: Antiport transport: like Na+ and glucose, Na+ and amino acids like Na+-H+ and Na+-K+ ā€¢ Secondary active transport : like H+ secretion
  • 58. Na+ active transport in PT epithelium
  • 59. ā€¢ Passway of transport Apical membrane, tight basolateral membrane Transcellular pathway juction, brush border, ā€¢ Na+ epithelium apical membrane Na+ pump peritubular capillary Paracellular transport ā€¢ Water, Cl- and Na+ tight juction peritubular capillary K+ Ca2+ and are reabsorpted with water by solvent drag
  • 60. The pathway of reabsorption
  • 61. Reabsorption of transcellular and paracellular pathway
  • 62. Location of reabsorption (Every parts of Nephron) ļ‚” Proximal tubule Brush border can reabsorption ļ‚” Henle's loop ļ‚” Distal tubule ļ‚” Collecting duct increase the area of
  • 63. Reabsorption and secretion in different part renal tubule of ā€¢ Proximal tubule (PT) 67% Na+, Cl-, K+ and water; 85% HCO3 - and 100% glucose and amino acids are reabsorbed H+ secretion 2/3 Transcellular pathway 1/3 Paracellular transport The key of reabsorption is Na+ reabsorption ( the action of Na+ pump in the membrane of proximal tubule).
  • 64. Na+ transcellular transportation in early part of PT epithelium
  • 65. Cl- passive reabsorption in later part of PT epithelium
  • 66. K+ reabsorption ļ‚” Most of in PT (70%)ļ¼Œ20% ļ‚” Active reabsorption in loop of Henle Ca2+ reabsorption ļ‚” 70% in PT , 20% in loop of Henle, 9% in DCT
  • 68. Glucose and amino acid reabsorption Glucose reabsorption: 99% glucose are reabsorbed, no glucose in urine ā€¢ Location: early part of PT Type of reabsorption: secondary active transport Renal glucose threshold When the plasma glucose concentration ā€¢ ā€¢ increases up to a value about 160 to 180 mg per deciliter, glucose can first be detected in the urine, this value is called the renal glucose threshold.
  • 69. Glucose secondary active transport in early part of PT
  • 70. Transport maximum (Tm) Transport maximum is the maximum rate at which the kidney active particular transport solute mechanisms can the transfer tubules. a into or out of Amino acid reabsorption: Location and type of reabsorption as same glucose as
  • 71. Glucose secondary active transport in early part of PT
  • 72. Co-transport of amino acids via Na+ symport mechanism.
  • 73. Loop of Henle: Ascending thick limb of loop of Henle Na+, Cl- and K+ cotransport Transportation rate: Na+ : 2Cl- : K+ Distal tubule and collecting duct: Principal cell: Reabsorption Na+ water and K+ secretion Intercalated cell: Secretion H+
  • 74. Secretion at the DCT ā€¢ ā€¢ DCT performs final adjustment of urine Active secretion or absorption Absorption of Na+ and Cl- Secretion of K+ and H+ based on blood pH ā€¢ ā€¢ ā€¢ ā€¢ Water is regulated by ADH (vasopressin) Na+, K+ regulated by aldosterone
  • 75. K+ H+ and secretion in distal tubule and collecting duct
  • 76. Co-transport of amino acids via Na+ symport mechanism.
  • 77.
  • 78. Summary of transport across PT , DT and collecting duct Proximal tubule Reabsorption Secretion filtered Na+ actively reabsorbed; Cl- follows passively. All filtered glucose and amino acids reabsorbed by secondary active transport, Filtered H2Oosmoticallyreabsorbed, Almost all filtered K+ reabsorbed, H+ Variable secretion, depending on acid-base status of body. Distal tubule and collecting duct Reabsorption Secretion Variable Na+ reabsorbed Aldosterone; Cl- follows passively. Variable H2O reabsorption, controlled by vasopressin (ADH) Variable H+ secretion, depending on acid-base status of body. by K+ Variable secretion, controlled by aldosterone.
  • 79. Urinary Concentration and Dilution Hypertonic urine: Lack of water in body can forms concentrated urine (1200 mOsm/L). Hypotonic urine: More water in body can forms dilute urine (50 mOsm/L). Isotonic urineļ¼šInjury of renal function Urinary dilution: The mechanism for forming a dilute urine is continuously reabsorbing reabsorb water. Urinary concentration: The basic requirements for forming a concentrated urine are a high fluid. ā€¢ ā€¢ ā€¢ ā€¢ solutes from the distal segments of the tubular system while failing to ā€¢ level of ADH and a high osmolarity of the renal medullary interstitial
  • 80. formation of dilute and concentrated urine.
  • 81. Control of Urine Volume and Concentration ā€¢ Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption Precise control allowed via facultative water reabsorption Osmolality ā€¢ ā€¢ ā€¢ ā€¢ The number of solute particles dissolved in 1L of water Reflects the solutionā€™s ability to cause osmosis ā€¢ ā€¢ Body fluids are measured in milliosmols (mOsm) The kidneys keep the solute load of body fluids constant at about 300 mOsm This is accomplished by the countercurrent mechanism ā€¢
  • 82. ļ‚” Formation of concentrated and diluted urine Drink more water in DCT and CD Lack of water in DCT and CD ADH diluted ADH water reabsorption urine. water reabsorption concentrated urine. ļ‚” Role of the vasa recta for maintaining the high solute concentration (NaCl and urea) in the medullary interstitial fluid. Role of countercurrent exchanger
  • 84. ā€¢ Basic structureļ¼š ā€œUā€type of loop of Henle Vasa rectaā€™s cliper type Collecting duct from cortex to medulla ā€¢ Basic functionļ¼š Different permeability of solutes and water DCT, CD and loop of Henle. in ā€¢ Osmotic gradient exit from cortex to medulla.
  • 85. Permeabilities of different segments of the renal tubule Segments of renal tubule Permeability water to Permeability to Na+ Permeability urea to Thick ascending limb Almost not Active transport of Na+, Secondary Almost not Cl- active Transport of Thin ascending limb Almost not Yes Moderate Almost not Almost not Thin descending limb Yes K+ Distal convoluted tubule Permeable Under ADH action Secretion of Almost not K+-Na+ exchange Collecting duct Cortex and outer Medulla almost not Inner medulla Yes Permeable Under ADH action Yes
  • 86. ļ‚” Mechanisms for creating osmotic gradient in the medullary interstitial fluid ļ‚” Formation of osmotic gradient is related to physiological characters of each part of renal tubule. ļ‚” Outer medullaļ¼š Water are permeated in descending thin limb, but not NaCl and urea. NaCl and urea are not water. permeated in ascending thin limb, but NaCl is active reabsorbed in ascending thick limb, but not Urea and water. ļ‚” Formation of osmotic gradient in outer medulla is due to NaCl active reabsorption in outer medulla.
  • 87. Inner medullaļ¼š High concentration urea exit in tubular fluid. ā€¢ ā€¢ ā€¢ Urea is permeated in CD of inner medulla in cortex and outer medulla NaCl is not permeated in descending thin NaCl is permeated in ascending thin limb Urea recyclingļ¼š but not ā€¢ ā€¢ ā€¢ ā€¢ limb Urea is permeated in ascending thin limb, part of urea into ascending thin limb from medulla and then diffusion to interstitial fluid again. Formation of osmotic gradient in inner medulla is due to urea recycling and NaCl passive diffusion in inner medulla. ā€¢
  • 88. Countercurrent Mechanism Interaction between the flow of filtrate through the loop of Henle (countercurrent multiplier) and the flow of blood through the vasa recta blood vessels (countercurrent exchanger) The solute concentration in the loop of Henle ranges from 300 mOsm to 1200 mOsm ā€¢ ā€¢
  • 89. ļ® Countercurrent exchange Countercurrent exchange is a common process in the vascular system. Blood flows in opposite directions along juxtaposed decending (arterial) and ascending (venous) vasa recta, and solutes and water are Exchanged between these capillary blood vessels. ļ® Countercurrent multiplication Countercurrent multiplication is the process where by a small gradient established at any level of the loop of Henle is increased (maltiplied) into a much larger gradient along the axis of the loop.
  • 90. Loop of Henle: Countercurrent Multiplication Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid ā€¢ ā€¢ ā€¢ Maintains the osmotic gradient Delivers blood to the cells in the area ā€¢ The descending loop: relatively impermeable to solutes, highly permeable to water The ascending loop: permeable to solutes, impermeable to water Collecting ducts in the deep medullary regions are permeable to urea ā€¢ ā€¢
  • 91. Countercurrent Multiplier and Exchange ā€¢ Medullary gradient osmotic ā€¢ H2Oļ‚®ECFļ‚®vasa recta vessels
  • 92. Formation of Concentrated ADH (ADH) is the signal to produce Urine ā€¢ concentrated urine inhibits diuresis This equalizes the osmolality of the filtrate and the interstitial fluid In the presence of ADH, 99% of the water in filtrate is reabsorbed it ā€¢ ā€¢
  • 93. Formation of Dilute Urine ā€¢ Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted Dilute urine is created by allowing this filtrate to continue into the renal pelvis Collecting ducts remain impermeable to water; no further water reabsorption occurs Sodium and selected ions can be removed by active and passive mechanisms Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma) ā€¢ ā€¢ ā€¢ ā€¢
  • 94. Figure 20-6: The mechanism of action of Mechanism of ADH (Vasopressin) Action: Formation of Water Pores ā€¢ ADH-dependent water reabsorption is called facultative water reabsorption vasopressin
  • 95. Water Balance Reflex: Regulators of Vasopressin Release Figure 20-7: Factors affecting vasopressin release
  • 96. Regulation of Urine Formation in the Kidney Way of regulation for urine formationļ¼š Filtration, Reabsorption and Secretion ā€¢ ā€¢ ā€¢ Autoregulation Solute concentration of tubular fluid Osmotic diuresis -- diabatic态mannitol Glomerulotubular balance ā€¢
  • 97. ļ‚” Nervous regulation ļ‚” Role of Renal Sympathetic Nerve ļ‚” Reflex of renal sympathetic nerve Reflex of cardiopumonary receptor renorenal reflex ļ‚” Renin-angiotention-aldosterone system
  • 99. Regulation by ADH ā€¢ Released by posterior pituitary when osmoreceptors detect an increase in plasma osmolality. Dehydration or excess salt intake: ā€¢ ā€¢ Produces sensation of thirst. Stimulates H20 reabsorption from urine. ā€¢
  • 100. The regulation of ADH secretion ļ¬ Source of ADH Hypothalamus supraoptic and paraventricular nuclei The change of crystal pressure osmotic Effective stimuli The change of effective blood volume
  • 102. Effects of ADH on the DCT and Collecting Ducts Figure 26.15a, b
  • 103. Regulation of ADH release: over hydration
  • 104. Regulation of release: hypertonicity
  • 105. Atrial Natriuretic Peptide Activity ļ¬ Increase GFR , reducing water reabsorption ļ¬ Decrease the osmotic gradient of renal medulla and promotes Na+ excretion ļ¬ Acting directly on collecting ducts to inhibit Na+ and water reabsorption, promotes Na+ and water excretion in the urine by the kidney ļ¬ Inhibition renin release and decrease angiotensin II and aldosterone, promotes Na+ excretion
  • 106. ļ‚” Endothelin (ET) Constriction blood vessels, decrease GFR ļ‚” Nitic Oxide (NO) Dilation blood vessels, increase GFR ļ‚” Epinephrine (EP), Norepinephrine (NE) promote Na+ and water reabsorption ļ‚” Prostaglandin E2 ,I2 Dilation blood vessels, excretion Na+ and water.
  • 107. A Summary of Renal Function Figure 26.16a
  • 108. Renal clearance 1. Concept: Renal clearance of any substance is the volume of plasma that is completely cleaned of the substance the kidneys per unit time (min) 2. Calculate concentration of it in urine Ɨurine volume by C = concentration of it in plasma
  • 109. Renal Clearance RC = UV/P RC = renal clearance rate U = concentration (mg/ml) of the substance in urine V = flow rate of urine formation (ml/min) P = concentration of the same substance Renal clearance tests are used to: in plasma ā€¢ ā€¢ Determine the GFR ā€¢ ā€¢ Detect glomerular damage Follow the progress of diagnosed renal disease
  • 110. Theoretical significance of clearance 3.1 Measure GFR ā€¢ A substance---freely filtered, non reabsorbed, non secreted--its renal clearance = GFR Clearance of inulin or creatinine can be used to estimate GFR ā€¢
  • 111. 3.2 Calculate RPF and RBF A substance--freely filtered, non reabsorbed, secreted completely from peritubular cells ---a certain concentration in renal arteries and 0 in venous. Clearance of para-aminohippuric acid (PAH) or diodrast can be used to calculate RPF .
  • 112. 3.3 Estimate of tubular handling for a substance If the clearance of substance>125ml/min? ---it must be secreted If it <125ml/min? --- it must be reabsorbed
  • 113. Physical Characteristics of Urine ļ¬ Color and transparency ā€¢ ā€¢ ā€¢ Clear, pale to deep yellow (due to urochrome) Concentrated urine has a deeper yellow color Drugs, vitamin supplements, and diet can change the color urine of ā€¢ pH ā€¢ ā€¢ Cloudy urine may indicate infection of the urinary tract ļ¬ Slightly acidic (pH 6) with a range of 4.5 to 8.0 Diet can alter pH ļ¬ Specific gravity ā€¢ ā€¢ Ranges from 1.001 to 1.035 Is dependent on solute concentration
  • 114. Chemical Composition of Urine ā€¢ ā€¢ Urine is 95% water and 5% solutes Nitrogenous wastes include urea, uric acid, creatinine Other normal solutes include: and ā€¢ ā€¢ ā€¢ Sodium, potassium, phosphate, and sulfate ions Calcium, magnesium, and bicarbonate ions ā€¢ Abnormally high concentrations of any urinary constituents may indicate pathology
  • 115. Urine Volume and Micturition 1. Urine volume ļ¬ ļ¬ Normal volume : 1.0~2.0L/day Obligatory urine volume ~400ml/day Minimum needed to excrete metabolic wastes of waste products in body. ļ¬ ļ¬ Oliguria--- urine volume < 400ml/day Anuria---urine volume < 100ml/day Accumulation of waste products in body. Polyuria--- urine volume > 2500ml/day long time Abnormal urine volume: Losing water and electrolytes. ļ¬
  • 116. Micturition Functions of ureters and bladder: Urine flow through ureters to bladder is propelled by contractions of ureter-wall smooth muscle. Urine is stored in bladder and intermittently ejected during urination, or micturition.
  • 117. Micturition ā€¢ Micturition is process of emptying urinary bladder Two steps are involved: the ā€¢ ā€¢ (1) bladder is filled progressively pressure rises until its ā€¢ ā€¢ above a threshold level (400~500ml); (2) a nervous reflex called micturition reflex occurs that empties bladder.
  • 118. Micturition ā€¢ Pressure-Volume curve of the bladder has a characteristic shape. There is a long flat segment as the initial increments of urine enter the bladder and then a sudden sharp rise as the micturition reflex is triggered. ā€¢
  • 119. Pressure-volume graph for bladder normal human 1.25 1.00 Sense of 0.75 0.50 0.25 100 200 300 400 Volume (ml) Pressure (kPa) Discomfort 1st desire urgency to empty bladder
  • 120. Micturition (Voiding or Urination) ā€¢ ā€¢ Bladder can hold 250 - 400ml Greater volumes stretch bladder walls initiates micturation reflex: Spinal reflex ā€¢ ā€¢ Parasympathetic stimulation contract Internal sphincter opens causes bladder to ā€¢ ā€¢ External sphincter relaxes due to inhibition
  • 122. Urination: Micturation reflex Figure 19-18: The micturition reflex
  • 123. Figure 25 Micturition (Voiding or Urination) .20a, b
  • 124. Review Questions Explain concepts 1.Glomerular filtration rate 2. Effective filtration pressure 3. Filtration fraction 4.Renal glucose threshold 5.Osmotic diuresis 6.Renal clearance
  • 125. Review Questions the functions of the kidneys? autoregulation of renal plasma 1. What are 2. Describe flow. 3. What are three basic processes for urine formation? 4. Describe the forces affecting glomerular filtration. 5. Describe the factors affecting GFR. 6. What is the mechanism of sodium reabsorption in the proximal tubules ?
  • 126. Review Questions 7. What is the mechanism of hydrogen ion secretion and bicarbonate reabsorption? What is the mechanism of formation of concentrated and diluted urine? After drinking large amount of water, what does 8. 9. the amount of urine change? Why? 10. Why a patient with diabetes has glucosuria and polyuria?